This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. More than 1.2 million Americans sustain a traumatic brain injury (TBI) annually, the majority of which are mild TBIs (MTBI) or cerebral concussions. Repeat concussions have been identified as a risk factor for the occurrence (or early expression) of neurodegenerative dementing disorders, including Mild Cognitive Impairment (MCI) and Alzheimer s disease (AD). The pathophysiology of these disorders is unclear and warrants further investigation. One particular area that has received little attention is the concept that repeat MTBI can lead to pituitary dysfunction (hypopituitarism) which in turn can be a direct cause of reduced general health, poor quality of life and sexual dysfunction. This linkage between TBI, hypopituitarism, reduced health and poor quality of life is already well-established for individuals sustaining a single moderate or severe TBI;recent studies indicate that these more severe TBIs lead to hypopituitarism in up to one third of individuals. We propose to study a cohort of retired NFL players who have documented poor quality of life to determine the relationship between these complaints, their concussion (MTBI) history, their pituitary hormonal function and sexual function. We hypothesize that the number of MTBIs sustained in their NFL career will correlate with the rate of hypopituitarism and that untreated hypopituitarism in these individuals will be associated with poor quality of life and general health, neuro-behavioral impairment and sexual dysfunction. This study will also determine the possible benefits of physiological hormone replacement therapy in retirees with diagnosed hypopituitarism.